US20060086689A1 - Method of fabricating microneedles - Google Patents
Method of fabricating microneedles Download PDFInfo
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- US20060086689A1 US20060086689A1 US10/972,196 US97219604A US2006086689A1 US 20060086689 A1 US20060086689 A1 US 20060086689A1 US 97219604 A US97219604 A US 97219604A US 2006086689 A1 US2006086689 A1 US 2006086689A1
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- microneedle
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
- C25D1/00—Electroforming
- C25D1/02—Tubes; Rings; Hollow bodies
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
- C25D1/00—Electroforming
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- the invention is generally related to microneedles and more particular to a method of fabrication thereof.
- microneedles In the medical field, hollow microneedles have been developed for delivering drugs or withdrawal of bodily fluids across biological barriers, such as skin.
- a microneedle is a miniature needle with a penetration depth of about 50-150 ⁇ m. The microneedle is designed to penetrate the skin but not hit the nerves.
- An array of microneedles may be combined with an analyte measurement system to provide a minimally invasive fluid retrieval and analyte sensing system.
- solid mironeedles are desirable as probles to sense electrical signals or to apply stimulation electrical signals, and hollow microneedles are useful as means for dispensing small volume of materials.
- microneedles require expensive processing steps.
- silicon is highly brittle and susceptible to fracturing during penetration.
- microneedles may be made from stainless steel and other metals.
- metal microneedles are subject to several disadvantages, one of which is the manufacturing complexities involved in metal processing steps such as grinding, deburring and cleaning. Therefore, there exists a need for a method of fabricating metal microneedles that is relatively simple and inexpensive.
- a fabrication method includes the steps of: providing a substrate; forming a metal-containing seed layer on the top surface of the substrate; forming a nonconductive pattern on a portion of the seed layer; plating a first metal on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening that exposes a portion of the nonconductive pattern, the opening having a tapered sidewall surface; plating a second metal onto the micromold to form a microneedle in the opening; separating the micromold with the microneedle formed therein from the seed layer and the nonconductive pattern; and selectively etching the micromold so as to release the microneedle.
- FIG. 1 is a flow chart illustrating a method for fabricating a microneedle in accordance with one embodiment of the present invention.
- FIGS. 2A-2F show cross-sectional views illustrating the method steps of FIG. 1 .
- FIG. 3 shows the cross-sectional view of a hollow microneedle being formed in accordance with another embodiment of the present invention.
- FIG. 4 is a flow chart illustrating a method for fabricating a microneedle in accordance with a third embodiment of the present invention.
- FIGS. 5A-5E show cross-sectional views illustrating the method steps of FIG. 4 .
- FIG. 6 is a flow chart illustrating a method for fabricating a microneedle with a sharp tip in accordance with a fourth embodiment of the present invention.
- FIGS. 7A-7F show cross-sectional views illustrating the method steps of FIG. 6 .
- FIG. 8 is a flow chart illustrating a method for fabricating a microneedle with a slanted tip in accordance with a fifth embodiment of the present invention.
- FIGS. 9A-9E show cross-sectional views illustrating the method steps of FIG. 8 .
- FIG. 1 is a flow chart illustrating a method for fabricating a microneedle in accordance with an embodiment of the present invention.
- a substrate is provided at step 100 .
- a metal-containing seed layer is formed on the substrate at step 101 .
- a nonconductive pattern is formed on a portion of the seed layer at step 102 .
- a first metal layer is plated on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening.
- a second metal is plated onto the micromold to form a microneedle in the opening at step 104 .
- the micromold together with the microneedle formed therein are separated from the seed layer and the nonconductive pattern at step 105 .
- the micromold is then selectively etched to release the microneedle at step 106 .
- FIGS. 2A-2F show the cross-sectional views illustrating the method steps of FIG. 1 .
- a metal-containing seed layer 2 is formed on a substrate 1 .
- the substrate 1 can be constructed from a semiconductor material such as silicon, a nonconductive material such as glass, a metal such as stainless steel or aluminum, or a premolded plastic.
- the metal-containing seed layer 2 may be a thin layer of chrome, stainless steel, tantalum or gold, which is formed by sputtering or other conventional deposition techniques.
- the seed layer 2 may also be a bilayer of chrome/stainless steel (chrome being the lower layer) or tantalum/gold (tantalum being the lower layer).
- the thickness for the seed layer may be between about 500 angstroms to about 20000 angstroms.
- a nonconductive layer is deposited on the seed layer 2 and patterned to produce a nonconductive pattern 3 as shown in FIG. 2B .
- the patterning of the nonconductive layer may be done by forming a photolithographic mask on the nonconductive layer followed by etching.
- Suitable materials for the nonconductive pattern 3 include silicon carbide, photoresist, silicon nitride, silicon oxide.
- the thickness for the nonconductive pattern may be between about 500 angstroms to about 50000 angstroms.
- a first metal is plated onto the seed layer 2 and over the edge of the nonconductive pattern 3 so as to form a micromold 4 with an opening 5 that exposes a portion of the nonconductive pattern 3 .
- the plating step may be done by electroplating, which can be controlled to generate an opening with a rounded and tapered sidewall 6 as shown in FIG. 2C .
- the first metal may be plated to a thickness between about 1 ⁇ m to 4 mm.
- the bottom of the opening 5 which defines the contour for the microneedle's tip to be formed, may have a diameter in the order of 5 ⁇ m to 100 ⁇ m.
- the micromold 4 may be constructed of any metal that can be electroplated with good uniformity during plating and can be selectively etched away with respect to other metals. Suitable metals include nickel, tin, tin-lead all, aluminium and aluminum alloys.
- a second metal is plated onto the micromold 4 so as to completely fill the opening 5 and form a microneedle 7 .
- the second metal used to form the microneedle 7 should be different from the first metal used for the micromold 4 .
- the microneedle may be constructed of a variety of metals depending on the intended use. For medical applications, the metal microneedle 7 may be made of palladium, silver, gold, nickel, brass, bronze, or alloys thereof.
- the properties of the second metal that are required for most applications include mechanical strength, biocompatibility, ability to be easily and uniformly electroplated into thick films, chemical stability (e.g. corrosion resistance), and ability to be selectively etched away from the first metal.
- nickel may be used for forming the micromold and silver may be used for forming the microneedle because palladium can be selectively etched from nickel using a solution nitric acid and hydrogen peroxide and it has high mechanical strength and is biocompatible and can be plated to a relatively thick film.
- the micromold 4 together with the microneedle 7 are separated from the seed layer 2 and the nonconductive pattern 3 .
- the separation may be done by peeling away the micromold 4 with the microneedle 7 formed therein.
- separation may be done with the aid of ultrasonic agitation. The whole structure is placed into a bath and ultrasonic energy is applied to induce mechanical vibration, thereby causing the separation.
- the micromold 4 is selectively etched to release the microneedle 7 as shown in FIG. 2F .
- the nickel micromold may be selectively etched away using a solution of nitric acid and hydrogen peroxide.
- the substrate 1 with the seed layer 2 and the nonconductive pattern 3 formed thereon ( FIG. 2B ) is a reusable structure upon which additional microneedles may be formed by repeating the plating steps.
- FIG. 2D shows that the second metal completely fills the opening 5 in the micromold 4 to form a solid microneedle 7 .
- the plating thickness of the second metal is controlled so as to form a plated coating on the sidewall of the opening 5 , thereby forming a hollow microneedle 8 .
- the second metal may be plated to a thickness in the range from about 5 ⁇ m to about 500 ⁇ m. Such hollow microneedles are useful for drug injection and extraction of bodily fluids.
- FIG. 4 is a flow chart illustrating a method for fabricating a microneedle in accordance with a third embodiment of the present invention.
- a substrate is provided at step 400 .
- a metal-containing seed layer is formed on the substrate at step 401 .
- a nonconductive pattern is formed on a portion of the seed layer at step 402 .
- a first metal layer is plated on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening.
- the micromold is separated from the seed layer and the nonconductive pattern at step 404 .
- a second metal is plated onto the micromold, thereby filling the opening and coating the exposed top and bottom surfaces of the micromold with the second metal.
- the micromold is selectively etched to release the plated second metal at step 406 .
- the plated second metal from step 406 has the configuration of a microneedle structure attached to an excess layer.
- the microneedle structure is then separated from the excess layer in step 407 .
- FIGS. 5A-5E show the cross-sectional views illustrating the method steps of FIG. 4 .
- a micromold 4 ′ having an opening 5 ′ is formed on a reusable structure composed of substrate 1 ′, seed layer 2 ′ and the nonconductive pattern 3 ′.
- the micromold 4 ′ is then separated from the reusable structure as shown in FIG. 5B .
- the separated micromold 4 ′ is next placed in a plating station and plating is carried out to fill the opening 5 ′ and cover the upper and lover surfaces of the micromold with a second metal 9 as shown in FIG. 5C .
- the micromold 4 ′ is then etched away leaving a microneedle structure 9 a attached to an excess layer 9 b as shown in FIG. 5D .
- the excess layer 9 b is separated from the microneedle structure 9 a by mechanical means.
- FIG. 6 is a flow chart illustrating the processing sequence for fabricating a microneedle with a sharp tip in accordance with a fourth embodiment of the present invention.
- a substrate having a recess in the top surface is provided at step 600 .
- a metal-containing seed layer is formed on the top surface at step 601 .
- a nonconductive pattern is formed on the seed layer at step 602 so that a portion of the nonconductive pattern is in the recess.
- a first metal layer is plated on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening.
- a second metal is plated onto the micromold to form a microneedle in the opening.
- the micromold together with the microneedle formed therein are separated from the seed layer and the nonconductive pattern at step 605 .
- the micromold is then selectively etched to release the microneedle at step 606 .
- FIGS. 7A-7F show the cross-sectional views illustrating the method steps of FIG. 6 .
- the starting structure is a silicon substrate 10 with a recess 11 , which defines the shape of the microneedle's tip to be formed.
- the recess 11 may be an inverted pyramidal recess or cone-shaped recess.
- the recess 11 is an etched pit formed by anisotropic wet etching using a solution containing tetramethyl ammonium. It will be understood by one skilled in the art that other techniques for forming a recess are possible.
- a tri-level seed layer 12 of tantalum-gold-tantalum is sputtered onto the silicon substrate 10 and a SiC pattern 13 is subsequently formed on top of seed layer 12 .
- the SiC pattern 13 is formed by d epositing a layer of SiC over the tantalum seed layer 12 followed by masking and etching.
- the SiC pattern 13 overlies the recess 11 as illustrated by the top view X in FIG. 7B .
- nickel is electroplated onto the tantalum-gold-tantalum seed layer 12 and over the edge of the SiC pattern 13 to form a micromold 14 with an opening 15 that is vertically aligned with the recess 11 as shown in FIG. 7C .
- the SiC pattern 13 is circular in shape, which shape gives rise to a convergent opening with circular cross section. It will be understood by one skilled in the art that other shapes are possible for the nonconductive pattern 13 .
- the micromold 14 together with the microneedle 16 are separated from the tantalum seed layer 12 and the SiC pattern 13 , e.g. by peeling.
- the nickel micromold 14 is then selectively etched away, e.g. using a solution of nitric acid and hydrogen peroxide, to release the microneedle 16 as shown in FIG. 7F .
- the microneedle 16 has a sharp, pointed tip 16 a.
- FIG. 8 is a flow chart illustrating the processing sequence for fabricating a microneedle with a slanted sharp tip in accordance with a fifth embodiment of the present invention.
- a substrate having a recess with an apex in the top surface is provided at step 800 .
- a metal-containing seed layer is formed on the top surface at step 801 .
- a nonconductive pattern is formed on the seed layer at step 802 so that a portion of the nonconductive pattern is in the recess.
- a first metal layer is plated on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening that is laterally offset from the apex.
- a second metal is plated onto the micromold to form a microneedle in the opening.
- the micromold together with the microneedle formed therein are separated from the seed layer and the nonconductive pattern at step 805 .
- the micromold is then selectively etched to release the microneedle at step 806 .
- the starting structure is a reusable structure composed of a silicon substrate 20 with an etched pit 21 , a tantalum-gold-tantalum seed layer 22 , and a SiC pattern 23 .
- the SiC pattern 23 is asymmetrically aligned relative to the apex 21 a of the etched pit 21 .
- nickel is electroplated onto the tantalum-gold-tantalum seed layer 22 and over the edge of the SiC pattern 23 to form a micromold 24 . This plating step results in a micromold 24 with an opening 25 that is offset from the apex 21 a due to the position of the nonconductive pattern 23 .
- microneedle 26 has a sharp and slanted tip 26 a. This needle configuration is particularly useful for extraction of biological fluids and delivery of drugs across the skin with minimal invasion.
- the microneedles fabricated by the above methods may have the following dimensions: a height in the range from about 2 ⁇ m to about 500 ⁇ m, a base diameter in the range from about 5 ⁇ m to about 1000 ⁇ m.
- the luminal diameter i.e., the diameter of the opening at the tip
- the luminal diameter is in the range from about 5 ⁇ m to about 150 ⁇ m.
- All of the above methods can be adapted to form an array of microneedles.
- the method steps are the same as described above except that an array of nonconductive patterns are formed on the seed layer, whereby the subsequent plating will result in a micromold with a plurality of openings instead of just one.
- microneedles fabricated by the above methods may be integrated with a measurement means to provide a fluid sampling and measurement device. Furthermore, the microneedles may be attached to a reservoir chamber that holds drugs to be delivered for therapeutic or diagnostic applications. Alternatively, the microneedles may be coated with a medication to be introduced into a body.
Abstract
Description
- The invention is generally related to microneedles and more particular to a method of fabrication thereof.
- In the medical field, hollow microneedles have been developed for delivering drugs or withdrawal of bodily fluids across biological barriers, such as skin. A microneedle is a miniature needle with a penetration depth of about 50-150 μm. The microneedle is designed to penetrate the skin but not hit the nerves. An array of microneedles may be combined with an analyte measurement system to provide a minimally invasive fluid retrieval and analyte sensing system. In other fields, solid mironeedles are desirable as probles to sense electrical signals or to apply stimulation electrical signals, and hollow microneedles are useful as means for dispensing small volume of materials.
- Methods for fabricating microneedles from silicon have been proposed. However, silicon microneedles require expensive processing steps. Furthermore, silicon is highly brittle and susceptible to fracturing during penetration. Alternatively, microneedles may be made from stainless steel and other metals. However, metal microneedles are subject to several disadvantages, one of which is the manufacturing complexities involved in metal processing steps such as grinding, deburring and cleaning. Therefore, there exists a need for a method of fabricating metal microneedles that is relatively simple and inexpensive.
- Low cost methods for fabricating microneedles are provided. A fabrication method according to one embodiment includes the steps of: providing a substrate; forming a metal-containing seed layer on the top surface of the substrate; forming a nonconductive pattern on a portion of the seed layer; plating a first metal on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening that exposes a portion of the nonconductive pattern, the opening having a tapered sidewall surface; plating a second metal onto the micromold to form a microneedle in the opening; separating the micromold with the microneedle formed therein from the seed layer and the nonconductive pattern; and selectively etching the micromold so as to release the microneedle.
- Other aspects and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings.
-
FIG. 1 is a flow chart illustrating a method for fabricating a microneedle in accordance with one embodiment of the present invention. -
FIGS. 2A-2F show cross-sectional views illustrating the method steps ofFIG. 1 . -
FIG. 3 shows the cross-sectional view of a hollow microneedle being formed in accordance with another embodiment of the present invention. -
FIG. 4 is a flow chart illustrating a method for fabricating a microneedle in accordance with a third embodiment of the present invention. -
FIGS. 5A-5E show cross-sectional views illustrating the method steps ofFIG. 4 . -
FIG. 6 is a flow chart illustrating a method for fabricating a microneedle with a sharp tip in accordance with a fourth embodiment of the present invention. -
FIGS. 7A-7F show cross-sectional views illustrating the method steps ofFIG. 6 . -
FIG. 8 is a flow chart illustrating a method for fabricating a microneedle with a slanted tip in accordance with a fifth embodiment of the present invention. -
FIGS. 9A-9E show cross-sectional views illustrating the method steps ofFIG. 8 . -
FIG. 1 is a flow chart illustrating a method for fabricating a microneedle in accordance with an embodiment of the present invention. In this embodiment, a substrate is provided atstep 100. A metal-containing seed layer is formed on the substrate atstep 101. A nonconductive pattern is formed on a portion of the seed layer atstep 102. Atstep 103, a first metal layer is plated on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening. Next, a second metal is plated onto the micromold to form a microneedle in the opening atstep 104. The micromold together with the microneedle formed therein are separated from the seed layer and the nonconductive pattern atstep 105. The micromold is then selectively etched to release the microneedle atstep 106. -
FIGS. 2A-2F show the cross-sectional views illustrating the method steps ofFIG. 1 . Referring toFIG. 2A , a metal-containingseed layer 2 is formed on asubstrate 1. Thesubstrate 1 can be constructed from a semiconductor material such as silicon, a nonconductive material such as glass, a metal such as stainless steel or aluminum, or a premolded plastic. The metal-containingseed layer 2 may be a thin layer of chrome, stainless steel, tantalum or gold, which is formed by sputtering or other conventional deposition techniques. Theseed layer 2 may also be a bilayer of chrome/stainless steel (chrome being the lower layer) or tantalum/gold (tantalum being the lower layer). The thickness for the seed layer may be between about 500 angstroms to about 20000 angstroms. - Next, a nonconductive layer is deposited on the
seed layer 2 and patterned to produce anonconductive pattern 3 as shown inFIG. 2B . The patterning of the nonconductive layer may be done by forming a photolithographic mask on the nonconductive layer followed by etching. Suitable materials for thenonconductive pattern 3 include silicon carbide, photoresist, silicon nitride, silicon oxide. The thickness for the nonconductive pattern may be between about 500 angstroms to about 50000 angstroms. - Referring to
FIG. 2C , a first metal is plated onto theseed layer 2 and over the edge of thenonconductive pattern 3 so as to form amicromold 4 with anopening 5 that exposes a portion of thenonconductive pattern 3. The plating step may be done by electroplating, which can be controlled to generate an opening with a rounded andtapered sidewall 6 as shown inFIG. 2C . The first metal may be plated to a thickness between about 1 μm to 4 mm. The bottom of theopening 5, which defines the contour for the microneedle's tip to be formed, may have a diameter in the order of 5 μm to 100 μm. Themicromold 4 may be constructed of any metal that can be electroplated with good uniformity during plating and can be selectively etched away with respect to other metals. Suitable metals include nickel, tin, tin-lead all, aluminium and aluminum alloys. - Referring to
FIG. 2D , a second metal is plated onto themicromold 4 so as to completely fill theopening 5 and form amicroneedle 7. The second metal used to form themicroneedle 7 should be different from the first metal used for themicromold 4. The microneedle may be constructed of a variety of metals depending on the intended use. For medical applications, themetal microneedle 7 may be made of palladium, silver, gold, nickel, brass, bronze, or alloys thereof. The properties of the second metal that are required for most applications include mechanical strength, biocompatibility, ability to be easily and uniformly electroplated into thick films, chemical stability (e.g. corrosion resistance), and ability to be selectively etched away from the first metal. For example, nickel may be used for forming the micromold and silver may be used for forming the microneedle because palladium can be selectively etched from nickel using a solution nitric acid and hydrogen peroxide and it has high mechanical strength and is biocompatible and can be plated to a relatively thick film. - Referring to
FIG. 2E , themicromold 4 together with themicroneedle 7 are separated from theseed layer 2 and thenonconductive pattern 3. The separation may be done by peeling away themicromold 4 with themicroneedle 7 formed therein. Alternatively, separation may be done with the aid of ultrasonic agitation. The whole structure is placed into a bath and ultrasonic energy is applied to induce mechanical vibration, thereby causing the separation. - Next, the
micromold 4 is selectively etched to release themicroneedle 7 as shown inFIG. 2F . If nickel is used to form themicromold 4, the nickel micromold may be selectively etched away using a solution of nitric acid and hydrogen peroxide. - The
substrate 1 with theseed layer 2 and thenonconductive pattern 3 formed thereon (FIG. 2B ) is a reusable structure upon which additional microneedles may be formed by repeating the plating steps. -
FIG. 2D shows that the second metal completely fills theopening 5 in themicromold 4 to form asolid microneedle 7. However, in another embodiment shown inFIG. 3 , the plating thickness of the second metal is controlled so as to form a plated coating on the sidewall of theopening 5, thereby forming ahollow microneedle 8. The second metal may be plated to a thickness in the range from about 5 μm to about 500 μm. Such hollow microneedles are useful for drug injection and extraction of bodily fluids. -
FIG. 4 is a flow chart illustrating a method for fabricating a microneedle in accordance with a third embodiment of the present invention. In this embodiment, a substrate is provided atstep 400. A metal-containing seed layer is formed on the substrate atstep 401. A nonconductive pattern is formed on a portion of the seed layer atstep 402. Atstep 403, a first metal layer is plated on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening. The micromold is separated from the seed layer and the nonconductive pattern atstep 404. Atstep 405, a second metal is plated onto the micromold, thereby filling the opening and coating the exposed top and bottom surfaces of the micromold with the second metal. The micromold is selectively etched to release the plated second metal atstep 406. The plated second metal fromstep 406 has the configuration of a microneedle structure attached to an excess layer. The microneedle structure is then separated from the excess layer instep 407. -
FIGS. 5A-5E show the cross-sectional views illustrating the method steps ofFIG. 4 . Referring toFIG. 5A , amicromold 4′ having anopening 5′ is formed on a reusable structure composed ofsubstrate 1′,seed layer 2′ and thenonconductive pattern 3′. Themicromold 4′ is then separated from the reusable structure as shown inFIG. 5B . The separated micromold 4′ is next placed in a plating station and plating is carried out to fill theopening 5′ and cover the upper and lover surfaces of the micromold with asecond metal 9 as shown inFIG. 5C . Themicromold 4′ is then etched away leaving amicroneedle structure 9 a attached to anexcess layer 9 b as shown inFIG. 5D . Referring toFIG. 5E , theexcess layer 9 b is separated from themicroneedle structure 9 a by mechanical means. -
FIG. 6 is a flow chart illustrating the processing sequence for fabricating a microneedle with a sharp tip in accordance with a fourth embodiment of the present invention. In this embodiment, a substrate having a recess in the top surface is provided atstep 600. A metal-containing seed layer is formed on the top surface atstep 601. A nonconductive pattern is formed on the seed layer atstep 602 so that a portion of the nonconductive pattern is in the recess. Atstep 603, a first metal layer is plated on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening. Next, atstep 604, a second metal is plated onto the micromold to form a microneedle in the opening. The micromold together with the microneedle formed therein are separated from the seed layer and the nonconductive pattern atstep 605. The micromold is then selectively etched to release the microneedle atstep 606. -
FIGS. 7A-7F show the cross-sectional views illustrating the method steps ofFIG. 6 . Referring toFIG. 7A , the starting structure is asilicon substrate 10 with arecess 11, which defines the shape of the microneedle's tip to be formed. As examples, therecess 11 may be an inverted pyramidal recess or cone-shaped recess. In an embodiment, therecess 11 is an etched pit formed by anisotropic wet etching using a solution containing tetramethyl ammonium. It will be understood by one skilled in the art that other techniques for forming a recess are possible. - Referring to
FIG. 7B , atri-level seed layer 12 of tantalum-gold-tantalum is sputtered onto thesilicon substrate 10 and aSiC pattern 13 is subsequently formed on top ofseed layer 12. TheSiC pattern 13 is formed by d epositing a layer of SiC over thetantalum seed layer 12 followed by masking and etching. TheSiC pattern 13 overlies therecess 11 as illustrated by the top view X inFIG. 7B . Next, nickel is electroplated onto the tantalum-gold-tantalum seed layer 12 and over the edge of theSiC pattern 13 to form amicromold 14 with anopening 15 that is vertically aligned with therecess 11 as shown inFIG. 7C . - In the embodiment of
FIG. 7B , theSiC pattern 13 is circular in shape, which shape gives rise to a convergent opening with circular cross section. It will be understood by one skilled in the art that other shapes are possible for thenonconductive pattern 13. - Referring to
FIG. 7D , palladium is electroplated onto themicromold 14 to form asolid microneedle 16 in theopening 15. Referring toFIG. 7E , themicromold 14 together with the microneedle 16 are separated from thetantalum seed layer 12 and theSiC pattern 13, e.g. by peeling. Thenickel micromold 14 is then selectively etched away, e.g. using a solution of nitric acid and hydrogen peroxide, to release themicroneedle 16 as shown inFIG. 7F . The microneedle 16 has a sharp, pointedtip 16 a. -
FIG. 8 is a flow chart illustrating the processing sequence for fabricating a microneedle with a slanted sharp tip in accordance with a fifth embodiment of the present invention. In this embodiment, a substrate having a recess with an apex in the top surface is provided atstep 800. A metal-containing seed layer is formed on the top surface atstep 801. A nonconductive pattern is formed on the seed layer atstep 802 so that a portion of the nonconductive pattern is in the recess. Atstep 803, a first metal layer is plated on the seed layer and over the edge of the nonconductive pattern to create a micromold with an opening that is laterally offset from the apex. Next, atstep 804, a second metal is plated onto the micromold to form a microneedle in the opening. The micromold together with the microneedle formed therein are separated from the seed layer and the nonconductive pattern atstep 805. The micromold is then selectively etched to release the microneedle atstep 806. - Referring to
FIG. 9A , the starting structure is a reusable structure composed of asilicon substrate 20 with an etchedpit 21, a tantalum-gold-tantalum seed layer 22, and aSiC pattern 23. TheSiC pattern 23 is asymmetrically aligned relative to the apex 21 a of the etchedpit 21. Referring toFIG. 9B , nickel is electroplated onto the tantalum-gold-tantalum seed layer 22 and over the edge of theSiC pattern 23 to form amicromold 24. This plating step results in amicromold 24 with anopening 25 that is offset from the apex 21 a due to the position of thenonconductive pattern 23. Next, silver is plated onto the sidewall surface of theopening 25 to create ahollow microneedle 26 as shown inFIG. 9C . Themicromold 24 andmicroneedle 26 are separated, e.g. by peeling, from the reusable structure as shown inFIG. 9D . Themicromold 24 is then selectively etched to release themicroneedle 26 as shown inFIG. 9E . The microneedle 26 has a sharp and slantedtip 26 a. This needle configuration is particularly useful for extraction of biological fluids and delivery of drugs across the skin with minimal invasion. - The microneedles fabricated by the above methods may have the following dimensions: a height in the range from about 2 μm to about 500 μm, a base diameter in the range from about 5 μm to about 1000 μm. For hollow microneedles, the luminal diameter (i.e., the diameter of the opening at the tip) is in the range from about 5 μm to about 150 μm.
- All of the above methods can be adapted to form an array of microneedles. In varying embodiments, the method steps are the same as described above except that an array of nonconductive patterns are formed on the seed layer, whereby the subsequent plating will result in a micromold with a plurality of openings instead of just one.
- The microneedles fabricated by the above methods may be integrated with a measurement means to provide a fluid sampling and measurement device. Furthermore, the microneedles may be attached to a reservoir chamber that holds drugs to be delivered for therapeutic or diagnostic applications. Alternatively, the microneedles may be coated with a medication to be introduced into a body.
- While certain embodiments have been described herein in connection with the drawings, these embodiments are not intended to be exhaustive or limited to the precise form disclosed. Those skilled in the art will appreciate that obvious modifications and variations may be made to the disclosed embodiments without departing from the subject matter and spirit of the invention as defined by the appended claims.
Claims (23)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/972,196 US7097776B2 (en) | 2004-10-22 | 2004-10-22 | Method of fabricating microneedles |
US11/420,764 US7785459B2 (en) | 2004-10-22 | 2006-05-28 | Microneedles and methods of fabricating |
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